Mycobacteria multiply in macrophages. Previous work has indicated that inhibition of TGF-beta production will limit the growth of intracellular pathogens including M. avium. This project will examine the potential of TGF-beta antagonists to affect the growth of M. tuberculosis (Mtb) in human macrophages. Studies will include the application of selected antagonists in combination with cytokines and the use of antagonists in vivo to limit infection and disease in mouse models of M. tuberculosis. PROPOSED COMMERCIAL APPLICATION: Sufficient evidence is available in animals models that TGF-beta antagonists may improve resistance to intracellular organisms. This may prove to be clinically useful and hence has good commercial potential.